肠道微生态与非酒精性脂肪性肝病研究进展

目的：运用网络药理学的方法,研究荔枝核提取物（Lychee kernel extract,LKE）干预非酒精性脂肪性肝病（Nonalcoholic fatty liver disease,NAFLD）的作用及分析潜在机制。方法：通过中药系统药理学数据库和分析平台（TCMSP）获取荔枝核的成分和作用靶点,通过疾病靶点数据Genecard获取NAFLD的疾病靶点,然后取交集,通过Cytoscape获取通路-靶点互作网络图,利用微生信网站进行 GO生物过程分析和 KEGG 通路富集分析。建立饮食诱导的肥胖（diet-induced obsisity,DIO）小鼠NAFLD动物模型并用LKE灌胃给药。HE染色观察肝脏脂质变化;试剂盒检测TG、TC、ALT、AST含量。结果：获得荔枝核潜在活性成分18个,与NAFLD疾病交集靶点52个,关键靶点为INS、TNF、HSP90AA1,通过KEGG通路富集筛选得到信号通路20条,主要为癌症通路（pathways in cancer）、动脉粥样硬化通路（Fluid shear stress and atherosclerosis）、糖尿病并发症的信号通路（AGE-RAGE signaling pathway in diabetic complications）;模型组小鼠肝脏病变严重,给药组小鼠肝脏病变相对于模型组明显减轻,给药组小鼠血清转氨酶也明显降低,接近正常组,给药组血脂代谢也趋于正常组,且差异均具有显著性（P<0.05）。结论：荔枝核可能通过作用于INS、TNF、HSP90AA1等靶点,调节脂质和动脉粥样硬化通路等起到治疗NAFLD的作用。     

茶多酚对高脂饮食诱导的非酒精性脂肪性肝病预防作用的研究进展

随着饮食习惯的改变和生活水平的提高，特别是高脂饮食的大量摄入，非酒精性脂肪性肝病（non-alcoholic fatty liver disease，NAFLD）发病率正在逐渐升高，西方发达国家平均发病率为20%～30%，我国平均发病率为15%～30%。NAFLD已经成为全球主要的公共卫生问题之一，严重威胁着人类的健康，其临床治疗仍然是一个挑战。茶多酚是从茶叶中提取出来的一种活性物质，其对人体健康有一定益处，特别是在一些常见疾病的预防作用方面具有较大潜力。为进一步系统了解茶多酚对NAFLD的作用，本文对茶多酚预防高脂饮食诱导的NAFLD的研究进展进行总结。     

四株益生菌对非酒精性脂肪性肝病的改善作用

探究了四株益生菌对非酒精性脂肪性肝病（Nonalcoholic Fatty Liver Disease,NAFLD）的改善作用。30只小鼠随机分为正常组（N）、高脂饮食（HFD）模型组（M）及益生菌干预组四组：植物乳杆菌LP45（Lactobacillus plantarum,LP）、嗜酸乳杆菌La28 （Lactobacillus acidophilus,La）、鼠李糖乳杆菌LR519（Lactobacillus rhamnosus,LR）和乳双歧杆菌BAL531（Bifidobacteriumlactis,Bal）。正常组给予常规饲料喂养,其它组给予HFD喂养;同时益生菌组每天给予对应菌液灌胃21 d,对照组给等体量生理盐水;期间监测小鼠体质量和摄食量。检测内脏脂肪、肝脏生化指标、组织病理和炎症因子表达水平。与N组相比,M组摄食量、体质量及内脏脂肪均显著增加,高达8.74 g/d、33.30 g、0.71 g。较于M组,益生菌干预组小鼠的摄食量和内脏脂肪均明显降低,Bal、La、LR和LP组摄食量分别为6.97、6.91、5.94和6.59 g/d;内脏脂肪0.41、0.40、0.27和0.36 g;ALT、CHO、TG和MDA水平也显著下降;肝脂肪变性明显缓解;炎症因子ELF3和TNF-α的mRNA及IL-6的蛋白表达水平显著降低（P<0.05）。体外,四株益生菌也表现出一定抗氧化和降脂活性,其中Bal抗氧化活性最高,达16.81%;La降脂活性最高,为46.40%。Bal、La、LP、LR可有效改善小鼠的NAFLD,其机制至少部分归因于其降脂、抗炎、抗氧化和保肝等生物学活性。     

玉米须水提物改善高脂饮食诱导大鼠非酒精性脂肪性肝病的研究

非酒精性脂肪性肝病(NAFLD)可增加肝硬化和肝癌的发病率,然而目前却没有特定的治疗药物.采用高脂饮食(High Fat Diet,HFD)喂养建立NAFLD大鼠模型,并同时灌胃给予玉米须水提物(corn silk aqueous extract,CSAE)进行干预,考察CSAE对NAFLD的抑制作用.实验结束后收集血...     

肠-肝轴介导的非酒精性脂肪性肝病及其营养干预研究进展

非酒精性脂肪性肝病（non-alcoholic fatty liver disease,NAFLD）是全球最常见的肝脏疾病。NAFLD始于肝脏脂质堆积,继而可能引起炎症,最终导致肝纤维化。有研究表明,肠道微生物及其产生的多种生物活性物质,通过门静脉与宿主肝细胞相互作用,进而导致NAFLD的发生发展,这种肠道和肝脏之间的双向通信,称为肠-肝轴。本文从肠道微生物组成、肠道屏障功能、肠道微生物成分、肠道微生物代谢物的角度阐述肠-肝轴介导NAFLD发生发展的作用机制,以及以肠-肝轴为靶点通过营养干预改善NAFLD;综述了肠道紊乱和NAFLD之间错综复杂相互作用的现有机制,以期为预防和改善NAFLD提供一定的营养策略。     

白萝卜提取物对大鼠非酒精性脂肪肝的药效作用

研究白萝卜提取物对大鼠非酒精性脂肪肝病的影响。实验用白萝卜提取物采用旋转蒸发的方法制备,使用脂肪乳剂灌胃法进行造模,设置低、中、高3个剂量处理组,分别以0.3、1、3mL/kg的剂量对SD大鼠进行灌胃。实验8周后观察各组大鼠的肝部组织病理学特点,并对血清中的脂类以及脂质过氧化相关酶类进行检测。结果显示：与模型组相比,雄性高剂量处理组大鼠血清甘油三酯(TG)以及丙二醛(MDA)水平明显降低,而还原性谷胱甘肽(GSH)明显增高。此外,肝脏病理切片显示白萝卜提取物有助于缓解脂肪在雄性大鼠肝中的积聚,而雌性大鼠的相关指标并无显著性差异。因此,白萝卜提取物可降低雄性非酒精性脂肪肝大鼠体内的脂质过氧化程度,从而起到延缓其非酒精性脂肪肝发展的作用。     

木瓜发酵液对非酒精性脂肪性肝病小鼠肝脏脂质代谢及AMPK/SIRT1通路的影响

目的:观察木瓜发酵液对高糖高脂饲料诱导的非酒精性脂肪性肝病（NAFLD）小鼠脂质代谢及AMP激活蛋白酶（AMPK）/沉默信息调节因子1（SIRT1）通路的调控机制。方法:取雄性昆明小鼠32只,随机分为4组,即正常组、模型组、木瓜发酵液高（10 m L/kg）和低剂量组（5 m L/kg）,每组8只。三周后,收集小鼠血液及组织样本。用试剂盒检测血清ALT、肝组织甘油三酯（TG）含量,分别用RT-PCR和Western Bloting检测p-AMPK和SIRT1基因的mRNA和蛋白表达水平。结果:与正常组比较,模型组小鼠病理证实肝组织脂质蓄积严重,血清ALT和肝脏TG水平明显升高（p<0.05）,肝组织SIRT1、Fox O1和p-AMPK mRNA及蛋白表达均显著降低（p<0.05）。与模型组比较,木瓜发酵液明显改善肝组织脂质蓄积,肝组织TG含量明显下降（p<0.05）,肝组织SIRT1、Fox O1 mRNA和SIRT1、p-AMPK蛋白表达均显著上调（p<0.05）,其中木瓜发酵液高剂量组较低剂量组效果好,但二者比较差异无统计学意义。结论:木瓜发酵液能够改善高糖高脂饮食诱导的NAFLD小鼠脂肪代谢紊乱,减轻肝脏脂质蓄积,其作用机制可能与肝细胞内AMPK/SIRT1通路的激活有关。      

木瓜提取物对小鼠脂肪肝的保护作用

本文研究了木瓜提取物对小鼠脂肪肝的干预作用。将40只雄性昆明小鼠随机分成4组,正常组、高脂组和药物低(100mg/kg)、高(300 mg/kg)剂量组。正常组给予普通饲料,高脂组给予高脂高糖饲料,用药组采用木瓜提取物低、高剂量饲料喂养,1月后处死,检测小鼠血清相关指标,HE染色观察肝脏组织形态,RT-PCR和激光共聚焦显微镜(Confocal)检测脂代谢相关基因表达,q PCR检测mi R-199a-5p水平。与正常组相比,高脂组小鼠血清中TC、ALT的水平增高;组织病理结果显示,肝脏脂肪变性明显;RT-PCR和Confocal结果显示,HGF、VEGFa和c-Met的表达降低,q PCR显示,高脂组中mi R-199a-5p水平增高。与高脂组比较,药物低、高剂量组脂肪肝病理损伤明显改善,血清ALT、TC含量均下降,HGF、VEGFa和c-Met表达水平上调,mi R-199a-5p水平降低。因此木瓜提取物对高脂高糖诱导的小鼠脂肪肝有保护作用,其可能的机制是通过调节mi R-199a-5p-HGF/c-Met信号通路发挥作用。     

天麻多糖对高脂饮食诱导的非酒精性脂肪肝的保护作用

目的:探讨天麻多糖对非酒精性脂肪肝的保护和延缓作用及其相关分子机制。方法:将60只ICR小鼠随机分成正常组、模型组、天麻多糖给药组(50、100和200 mg/kg),除正常组给予普通饲料外,其余各组给予高脂饲料以诱导模型。同时,按剂量给予相应的药物,每 d 1次,持续10周。末次给药后30 min,记录小鼠体重及脏器指数,通过组织病理学方法评估肝脏组织的病理变化,分别测定小鼠血清天冬氨酸氨基转移酶（Aspartate amino transferase,AST）、丙氨酸氨基转移酶（Alanine amino transferase,ALT）活力,并同时检查与氧化应激损伤和脂质代谢相关的信号转导途径。结果:与模型组相比,天麻多糖可显著降低血清中AST和ALT活性（P<0.05）,减轻脂肪肝组织病理损伤症状,同时调节多种与脂质积累相关的基因表达水平改善脂质代谢（P< 0.05）;此外,天麻多糖还通过上调Nrf2/GPx信号途径改善氧化应激损伤（P<0.05）,抑制肝组织中NF-κB、TNF-α、IL-1β以及与炎症反应相关的iNOS和COX-2蛋白表达（P<0.05）,并同时可抑制Bax表达,上调Bcl-2因子（P<0.05）。结论:天麻多糖可以改善小鼠的肝功能,调节脂质代谢水平减少脂肪堆积,同时缓解肝脏氧化应激损伤和抑制炎症来保护和延缓高脂饮食引起的非酒精性脂肪肝症状。     

刺梨多糖对非酒精性脂肪肝小鼠回肠黏膜屏障功能的影响

为研究刺梨多糖（Rosa roxburghii Tratt polysaccharides,RTFP）对非酒精性脂肪肝（non-alcoholic fatty liver disease,NAFLD）诱导的小鼠回肠肠道黏膜屏障功能障碍和肠道炎症的改善作用,以及刺梨多糖对肠道菌群的影响,本研究采用高脂肪饮食（high fat diet,HFD）喂养小鼠,构建NAFLD小鼠模型,然后灌胃RTFP,干预7周。结果表明,RTFP可显著降低NAFLD诱导的小鼠回肠炎症因子和氧化应激水平,改善脂质代谢紊乱状况。微观组织病理学观察发现,RTFP可以使小鼠回肠结构形态趋向于正常水平,减少隐窝病变,保护肠道屏障。通过16S rRNA高通量测序评估各处理组小鼠粪便微生物群的变化,发现RTFP可调节NAFLD小鼠肠道菌群的多样性和组成,厚壁菌门（Firmicutes）与拟杆菌门（Bacteroidetes）比值明显降低,提高了有益菌群的相对丰度,降低了病原菌群的相对丰度。RTFP可以作为一种益生元调节肠道菌群,改善NAFLD模型小鼠的肠道微生态,减轻肠道屏障功能障碍,维持肠道正常功能。     

Chemoprevention of nonalcoholic fatty liver disease by dietary natural compounds

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease that is not from excess alcohol consumption, but is often associated with obesity, type 2 diabetes, and metabolic syndrome. NAFLD pathogenesis is complicated and involves oxidative stress, lipotoxicity, mitochondrial damage, insulin resistance, inflammation, and excessive dietary fat intake, which increase hepatic lipid influx and de novo lipogenesis and impair insulin signaling, thus promoting hepatic triglyceride accumulation and ultimately NAFLD. Overproduction of proinflammatory adipokines from adipose tissue also affects hepatic metabolic function. Current NAFLD therapies are limited; thus, much attention has been focused on identification of potential dietary substances from fruits, vegetables, and edible plants to provide a new strategy for NAFLD treatment. Dietary natural compounds, such as carotenoids, omega‐3‐PUFAs, flavonoids, isothiocyanates, terpenoids, curcumin, and resveratrol, act through a variety of mechanisms to prevent and improve NAFLD. Here, we summarize and briefly discuss the currently known targets and signaling pathways as well as the role of dietary natural compounds that interfere with NAFLD pathogenesis.     

粉葛多糖改善金黄地鼠非酒精性脂肪肝及对肠道菌群的调节作用

目的 研究粉葛多糖对高脂饮食诱导的金黄地鼠非酒精性脂肪肝(nonalcoholicfattyliverdisease,NAFLD)的改善作用及与肠道菌群的关系。方法 金黄地鼠随机分为空白组、高脂模型组、粉葛多糖高剂量组(100 mg/kg)、粉葛多糖低剂量组(50 mg/kg)。15周后,测定肝脏质量、肝指数、血脂及脂多糖(lipopolysaccharide,LPS)水平,肝脏及结肠切片苏木素-伊红染色,结肠内容物16S rRNA测序。结果 与高脂模型组相比,粉葛多糖显著降低了肝脏质量及肝指数,改善了总胆固醇、低密度脂蛋白胆固醇水平,甘油三酯及LPS水平显著降低,可改善肠道屏障损伤及肝脏脂肪变性;在肠道菌群门水平上,粉葛多糖能降低肠源性LPS主要来源菌门Proteobacteria的相对丰度至0.05%,在属水平上,粉葛多糖能促进与肥胖呈负相关的Parabacteroides及与肠道黏膜修复相关的Lachnospiraceae NK4A136 group富集。结论 粉葛多糖可能通过调节肠道菌群改善高脂饮食诱导的金黄地鼠NAFLD。     

马尾松花粉提取物对小鼠非酒精性脂肪肝的预防作用

目的研究马尾松花粉提取物对小鼠非酒精性脂肪肝的预防作用,并探讨潜在的作用机制。方法将60只小鼠随机分为空白对照组、高脂模型组、低剂量(20 mg/kg·d)、中剂量(40 mg/kg·d)和高剂量(80 mg/kg·d)马尾松花粉提取物组及葵花护肝片组(0.7 g/kg·d),马尾松花粉提取物组灌胃相应剂量的马尾松花粉提取物,连续2周给予高脂鼠粮,同时灌胃相应受试物,空白对照组和模型组给予同体积生理盐水。实验结束后检测小鼠血清中丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、超氧化物歧化酶(superoxide dismutase,SOD)活性和低密度脂蛋白(low-density lipoprotein,LDL-C)、高密度脂蛋白(high density lipoprotein,HDL-C)、甘油三酯(triglycerides,TG)及总胆固醇(total cholesterol,TC)水平;并检测肝组织中还原性谷胱甘肽(glutathione,GSH)和丙二醛(malondialdehyde,MDA)含量及SOD活性。结果松花粉提取物明显降低高脂饮食所致小鼠血清ALT、AST活性以及TG、TC、LDL-C水平(P0.05),提高SOD活性及HDL-C含量;同时小鼠肝组织MDA含量显著下降,GSH含量提高,SOD活性升高(P0.05)。病理学结果显示,MPPE能显著减轻肝脏病理学损伤程度,表现为肝细胞脂肪变性及炎症的减轻。结论松花粉提取物对小鼠非酒精性脂肪肝具有明显的保护作用,其机制可能与抗氧化有关,并且具有剂量依赖性。     

Effects and molecular mechanisms of Ninghong black tea extract in nonalcoholic fatty liver disease of rats

The aim of this study is to observe the effects of Ninghong black tea extract on fat deposition and high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) and to explore the potential mechanisms of these effect. Under 2% Ninghong black tea extract diet feeding in rat model, the results showed that Ninghong black tea extract decreased the body fat ratio and the number of lipid droplets in the liver and significantly alleviated NAFLD in the rat model. The real-time fluorescence quantitative polymerase chain reaction results showed that Ninghong black tea extract significantly upregulated the expression of peroxisome proliferator-activated receptor α (PPARα), which is important in fatty acid β-oxidation, and microsomal triglyceride transfer protein (MTP), which plays an important role in the synthesis of very low density lipoprotein (VLDL). By promoting the expression of PPARα and MTP in liver tissue and thereby promoting fatty acid β-oxidation and VLDL synthesis, Ninghong black tea extract relieves high-fat diet-induced NAFLD.     

膳食油脂与非酒精性脂肪肝病形成相关研究进展

市场中的膳食油脂产品琳琅满目,消费者在选择食用油的过程中通常会考虑其对健康的影响,尤其是广泛流行的营养代谢性疾病非酒精性脂肪肝病（NAFLD）。我国NAFLD的患病率持续增长,给个人和社会造成巨大的压力。大量的研究表明,膳食油脂与NAFLD的形成关系密切,合理的膳食用油能有效预防NAFLD。通过对油脂脂肪酸链长、饱和度及双键位置、奇偶性与NAFLD形成的相关研究进行梳理,结合饮食模式综述了膳食油脂与NAFLD形成相关研究进展,以期为学术探索和日常膳食油脂提供依据。     

Beneficial effects of Lactobacillus rhamnosus hsryfm 1301 fermented milk on rats with nonalcoholic fatty liver disease

A growing stream of research suggests that probiotic fermented milk has a good effect on nonalcoholic fatty liver disease. This work aimed to study the beneficial effects of Lactobacillus rhamnosus hsryfm 1301 fermented milk (fermented milk) on rats with nonalcoholic fatty liver disease induced by a high-fat diet. The results showed that the body weight and the serum levels of total cholesterol, total glyceride, low-density lipoprotein, alanine transaminase, aspartate aminotransferase, free fatty acid, and reactive oxygen species were significantly increased in rats fed a high-fat diet (M) for 8 wk, whereas high-density lipoprotein cholesterol and superoxide dismutase were significantly decreased. However, the body weight and the serum levels of total cholesterol, total glyceride, alanine transaminase, aspartate aminotransferase, free fatty acid, reactive oxygen species, interleukin-8, tumor necrosis factor-α, and interleukin-6 were significantly decreased with fermented milk (T) for 8 wk, and the number of fat vacuoles in hepatocytes was lower than that in the M group. There were significant differences in 19 metabolites in serum between the M group and the C group (administration of nonfermented milk) and in 17 metabolites between the T group and the M group. The contents of 7 different metabolites, glycine, glycerophosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, thioetheramide-PC, d-aspartic acid, oleic acid, and l-glutamate, were significantly increased in the M group rat serum, and l-palmitoyl carnitine, N6-methyl-l-lysine, thymine, and 2-oxadipic acid were significantly decreased. In the T group rat serum, the contents of 8 different metabolites—1-O-(cis-9-octadecenyl)-2-O-acetyl-sn-glycero-3-phosphocholine, acetylcarnitine, glycine, glycerophosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, d-aspartic acid, oleic acid, and l-glutamate were significantly decreased, whereas creatinine and thymine were significantly increased. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that 50 metabolic pathways were enriched in the M/C group and T/M group rat serum, of which 12 metabolic pathways were significantly different, mainly distributed in lipid metabolism, amino acid, and endocrine system metabolic pathways. Fermented milk ameliorated inflammation, oxygenation, and hepatocyte injury by regulating lipid metabolism, amino acid metabolic pathways, and related metabolites in the serum of rats with nonalcoholic fatty liver disease.     

辣木籽提取物对高脂血症小鼠血脂及肝脏的影响北大核心CSCD

通过向高脂血症模型小鼠灌胃辣木籽提取物,研究辣木籽提取物对高脂血症小鼠血脂及肝脏的影响。将60只KM小鼠按体质量随机分为正常组,模型组,辛伐他汀组(1 mg/kg),辣木籽提取物低(5 mg/kg)、中(10 mg/kg)、高(20 mg/kg)剂量组,每组10只。除正常组饲喂基础饲料外,其余各组小鼠以高脂饲料连续喂养。实验第6周开始,除正常组和模型组外,其余各组小鼠灌胃给予相应药物,连续3周。实验结束后测定各组小鼠血清HDL-C、LDL-C、 TG、TC水平;剖取肝脏,测定肝脏指数并进行病理形态学观察;采用免疫组化法检测肝脏组织法尼酯X受体(FXR)蛋白的表达水平。结果表明:低、中、高剂量辣木籽提取物可显著降低高脂血症小鼠血清TG、TC及LDL-C水平(p<0.05),极显著升高HDL-C水平(p<0.01),改善小鼠肝脏病理形态,极显著降低小鼠肝脏病理评分(p<0.01);低剂量辣木籽提取物可显著降低小鼠肝脏指数,低、中剂量辣木籽提取物可显著降低肝脏FXR蛋白的表达(p<0.05)。因此,一定剂量的辣木籽提取物对高脂血症小鼠具有显著的治疗作用,其作用机制可能与下调FXR蛋白表达有关。